Complelent and Its Fractions (C3 - C4) Pattern in Subjects with Msoplasia

The total complement (CH₅₀) and its fractions C₃ and C₄ have been assayed for up to two years after surgery in subjects with breast, gastric and colon-rectum carcinomas. In all three types of pathology a constant pattern has been observed. Before surgery the CH₅₀ stayed below the normal range but was increased following surgery. After a month it was again within the nomal. range and subsequently, according to the clinical. evolution of the disease, it remained normal in those patients without relapse or any apparent metastasis, whereas in those patients who displayed metastatis and/or approached the terminal phase it fell below the normal range. The C₃ fraction followed the CH₅₀ pattern whereas the C₄ did not show any variation correlated with the stages of the disease.     

Pancreatic phospholipase A2 induces bacterial translocation in rats

The importance of pancreatic enzymes, particularly phospholipase A₂ (PLA₂), for bacterial translocation, which is considered to be one of the aggravating causes of acute pancreatitis, was investigated. Male rats were administered an intraperitoneal or intravenous injection of normal saline, PLA₂, or amylase. Four days later, the mesenteric lymph nodes (MLNs) and portal blood of the animals were cultured. None of the animals had a positive portal blood culture. The MLNs contained enteric bacteria in 78 % of the animals given 50 mg/kg of PLA₂ intraperitoneally. 5 mg/kg of PLA₂ intraperitoneally, 50 mg/kg of amylase intraperitoneally, or 50 mg/kg of PLA₂ intravenously showed positive cultures in 25 %, 20 %, and 11 %, respectively. None of the animals given intraperitoneal or intravenous normal saline had positive cultures of their MLNs. Intraperitoneal injection of 25mg/kg of nafamostat mesilate just before intraperitoneal PIA₂ (50 mg/kg) resulted in a reduction of positive MLNs from 70 % to 30 %. The cecal myeroperoxidase (MPO) activity of animals administered 50 mg/kg of PIA₂ intraperitoneally was significantly higher compared with animals administered saline intraperitoneally. These results indicate that intraperitoneal leakage of PLA₂ plays an important role in bacterial translocation during acute pancreatitis and that administration of a protease inhibitor may be effective against the bacterial translocation.     

The Effect of Prostaglandin E1 or E2 OH the in Vitro Blastogenic Response of Lymphocytes from Normal and Tumor-Bearing Mice

The in vitro effect of exogenously added prostaglandin (PG) El or E₂ over concentrations ranges of from 1 × 10^--⁴ to 1 × 10-9 M were studied in order to determine their effect on the in vitro lymphocyte proliferation of thymic and splenic T and B cells from normal and tumor-bearing CD₂ F ₁ mice. It was found that PGE₁ generally caused greater inhibition of blastogenesis than did PGE₂ when reacted with splenic lymphocytes from normal mice. Indeed, PGE₂ was found to be stimulatory for both Con A^- and LPS-sensitive normal splenic lymphocytes. Both PGE_l and PGE₂ caused potent inhibition of Con A^- and PHA-sensitive splenic lymphocytes from the tumor-bearing mice. Additionally, PGE₂ was found to stimulate the LPS-reactive lymphocytes from the tumored mice. PGE₁ and PGE₂ both inhibited the Con A- and PHA-reactive thymic lymphocytes from normal mice at the lower concentrations studied, i.e., 10^--⁴ to 10^--⁶ M. Thereafter, at concentration ranoes of from 10^--⁷ to 10^--⁹ M both PGE₁ and PGE₂ were both found to be stimulatory. Finally, both PGE₁ and PGE₂ at all concentrations studied, strongly inhibited the thymic lymphocytes from tumored mice.     

纳米TiO2:C薄膜涂层的生物相容性评价

背景：前期实验采用溶胶-凝胶法在纯钛片表面制备了纳米TiO₂:C薄膜涂层。 目的：评估纳米TiO₂:C薄膜涂层的生物相容性。 方法：①溶血实验：取新西兰大白兔静脉血,分别加到TiO₂-生理盐水、TiO₂:C-生理盐水、蒸馏水和生理盐水中。②细胞毒性实验：将TiO₂:C浸提液加入对数生长期的L929 细胞培养基中。③短期全身毒性实验：将60只BALB/C小白鼠随机分为3组,分别灌胃给予TiO₂浸提液、TiO₂:C浸提液及生理盐水。④口腔黏膜刺激实验：将牙胶圆片与TiO₂:C纳米薄膜涂片分别缝合固定于仓地鼠颊黏膜上。 结果与结论：纳米TiO₂:C涂层未引起急性溶血,毒性等级为0-1 级,未对细胞产生明显毒性,细胞周期未见明显异常;TiO₂:C浸提液对小鼠无短期全身毒性;对仓鼠口腔黏膜无刺激性。表明纳米TiO₂:C薄膜涂层具有良好的生物安全性。     

Serum complement changes in W/Fu rats inoculated with syngeneic (C58NT) D lymphoma cells

Weanling W/Fu rats were inoculated intraperitoneally with 1 X 10(6) to 1 X 10(7) (C58NT)D Gross virus-induced lymphoma cells. Sera obtained 7 days later showed moderate to marked depressions of overall hemolytic activity, C1, C3 and properdin. These changes were not observed in uninjected W/Fu rats or in animals inoculated with syngeneic normal spleen cells. In the latter group and in the tumor-bearing animals, factor B levels were also depressed. Evidence of complement utilization was also observed in the ascitic fluids of the tumor-bearing W/Fu rats.     

Non-enzymic activation of the fifth component of human complement, by oxygen radicals. Some properties of the activation product, C5b-like C5

Purified human C5 was converted non-enzymically to an activated form as defined by its ability to participate in reactive lysis. This conversion occurred following exposure to systems that generate oxygen radicals, namely addition of H₂O₂ in the presence of ascorbic acid and iron or the addition of xanthine oxidase, acetaldehyde and iron. The conversion of C5 to a functionally active species was iron-dependent and inhibited by hydroxyl radical scavengers such as DMSO. The findings suggest that OH is the active oxygen species that converts C5. The conversion product of C5, termed C5(H₂O₂), is C5b-like due to its ability to bind C6 and cause reactive lysis. C5(H₂O₂) is much more stable than C5b obtained by complement convertases. Although C5(H₂O₂) has lost the binding site of native C5 for C3b it can be cleaved by complement-derived convertases; the cleavage is, however, less efficient than in the case of native C5. The resulting cleavage product, which is C5a-like, is chemotactic although C5(H₂O₂) is not chemotactic. C5(H₂O₂) serves as a better substrate for plasma kallikrein than native C5, resulting in the generation of a C5a-like chemotactic product. These data indicate that oxygen radicals can bring about a conformational change in C5, causing it to behave as a functionally activated molecule of the complement system. This may have implications for the role of complement and its activation in the inflammatory response.     

A high incidence of C9 deficiency among healthy blood donors in Osaka, Japan

By the use of sucrose gelatin veronal buffer (SGVB), a simple screening test was developed by us to detect sera with low complement activity, including C9-deficient sera. Using this screening test, we were able to identify sera with low complement activity including C9-deficient sera among a large number of samples. Further examinations, estimation of the protein concentration of C9, C4, C3, etc., enabled classification of serum with low complement activity into C9-deficient serum, serum deficient in the other components, and serum with low complement activity caused by non-specific activation of complement through the classical pathway by low temperature in vitro. Among 145,640 sera from Osaka donors, 138 sera were found to be deficient in C9 by these methods. The whole complement activity (CH50) of the 138 sera was 13.1 +/- 3.0 U/ml. The C9 protein in these sera was undetectable, not only by the single radial immunodiffusion method, but also by the sensitive ELISA method. C9 activities in these sera were less than 0.1% of the level in pooled normal human serum. These findings and the family studies revealed that 138 blood donors unquestionably had a hereditary C9 deficiency. The incidence of C9 deficiency among Osaka donors was calculated to be 0.095%.     

Hereditary C6 deficiency in a strain of PVG/c rats.

A chance observation has led to the discovery of a strain of PVG rats (PVG/c-) which are deficient in complement (C) component C6. Analysis of total haemolytic activity (CH50) of PVG/c- serum revealed an absent CH50 activity compared with serum of other rat strains and of a PVG/c rat (PVG/c+) that showed normal C activity. Thus, the PVG/c- rat was unable to activate the C5b-9 membrane attack complex. To gain insight into the complement abnormalities, analysis of individual C components was performed. Testing the PVG/c- serum in a C6 haemolytic assay and using deficient human sera showed a deficiency of C6 in the PVG/c- rat. Highly purified human C6 and human sera deficient in other components were able to reconstitute the CH50 activity of the PVG/c- rat. The possibility that an inactivator of C was present in PVG/c- serum was excluded. The deficiency was found to be inheritable and under the control of an autosomal recessive gene. Furthermore, tissue antigens and immunity of the PVG/c- rat were found to be identical to those determined in the PVG/c+ rat. With regard to their health status, the PVG/c- animals seem to have no disadvantages compared with PVG/c+ rats when held under the same conditions within the protected environment of animal facilities. Taken together, both rat strains provide an unique animal model for studying the biological role of C, particularly the C5b-9 membrane attack complex in experimental medicine.     

Human F(ab')2-containing immune complexes together with anti-hinge natural antibodies stimulate complement amplification in vitro and in vivo

The systemic inflammatory response syndrome (SIRS) is triggered by C5a generation following an excessive complement amplification, but it has remained unclear how complement amplification is stimulated. It is known that neutrophilic elastase can cleave IgG to F(ab′)₂ and that F(ab′)₂-containing immune complexes (F(ab′)₂-IC) stimulate complement amplification together with an unidentified plasma factor. We show that absorption of plasma on F(ab′)₂ from human IgG removed this factor and prevented F(ab′)₂-IC from stimulating complement amplification. The required factor was purified from pooled whole human IgG (IVIG) as those naturally occurring antibodies (NAbs) that bind to F(ab′)₂, but not to intact IgG. These “anti-hinge NAbs” restored complement amplification by F(ab′)₂-IC in absorbed plasma. Anti-hinge NAbs must have formed secondary, rigidified IC from F(ab′)₂-IC, because the F(ab′)₂ fragments evidently captured dimeric C3b, known as a potent C3 convertase precursor. This process may also stimulate complement amplification in vivo, because plasma from septic patients at the onset of SIRS indeed contained F(ab′)₂ fragments. The concentrations of F(ab′)₂ and that of factor Bb, an unbiased measure of complement amplification, correlated linearly with that of released elastase. Moreover, the F(ab′)₂ fragments migrated on gelfiltration columns together with anti-hinge NAbs as ICs with MW of up to 750 kDa, as verified on plasma of each of the nine patients studied. These findings provide for the first time a plausible mechanism of how F(ab′)₂-containing immune complexes stimulate complement amplification together with anti-hinge NAbs. The same mechanism may contribute to complement overreaction at the onset of SIRS.     

Alternative Non-Immune F(ab')2-Mediated Immunoglobulin Binding to Group C and G Streptococci

We tested 140 bacterial strains representing 19 different species for binding or purified radiolabelled F(ab')₂ fragments prepared by pepsin digestion of polyclonal and monoclonal human IgG. Both polyclonal and monoclonal F(ab')₂ fragments showed positive binding to group C and G streptococci with maximum uptake levels of 50% and 85%. Binding was obtained both with fresh bacteria and with organisms stabilized by heat treatment. F(ab')₂ fragments of two human IgG1 myeloma proteins with anti-staphylolysin specificity showed a similar binding pattern. IgG present in normal human serum inhibited the uptake of F(ab')₂ fragments, whereas albumin and fibrinogen and purified Fc fragments prepared by papain digestion of polyclonal IgG and monoclonal IgG1 did not show such capacity. Fourteen human myeloma proteins representing IgA, IgM and the four IgG subclasses were tested for inhibiting capacity. Reactivity was noted with at least one myeloma protein within each IgG subclass but not with IgA or with IgM monoclonal proteins. Normal rabbit serum was as inhibitory as normal human serum, whereas dog serum was less reactive. These data demonstrate that group C and G streptococci carry a heat-stable surface component interacting with the F(ab')₂ portion of the IgG molecule. The results suggest that the reactive site on the immunoglobulin molecule may reside in the more constant part of the variable domain. This new reactivity is different from the previously known non-immune reaction involving the IgG Fc portion. This alternative non-immune reactivity is analogous to but distinct from the alternative protein A reaction in Staphylococcus aureus .     

Role of complement C9 and calcium in the generation of arachidonic acid and its metabolites from rat polymorphonuclear leukocytes

We have previously shown that antibody-sensitized mouse peritoneal macrophages release arachidonic acid (C20:4) and its oxygenated derivatives when treated with complement, and that the major part of the release depended on the terminal complement complexes (TCC). To further delineate the process(es) responsible for this release we have extended our studies to rat peritoneal poly-morphonuclear leukocytes (PMNs). Experiments were performed with antibody-sensitized rat PMNs labeled with [³H]C20:4 and carrying the TCC, C5b-7, C5b-8 or C5b-9. In contrast to the results of other studies, production of leukotriene B₄ (LTB₄), the major radiolabeled derivative, was strictly dependent on the presence of C9. However, low levels of C20:4 and prostaglandins (PGs) were produced prior to the C5b-9 stage. Kinetic studies demonstrated that release of LTB₄ was rapid; the initial release occurred within 4–6 min and a second rise in release coincided with cell death. Virtually all the LTB₄ produced was released as we found no evidence of retention of intracellular LTB₄ at either the C5b-8 or C5b-9 stages. In the absence of extracellular calcium, the release of LTB₄ was completely abolished and the release of C20:4 and PGs was drastically reduced. [³H]C20:4-labeled PMNs carrying C5b-9 did release substantial amounts of radiolabeled material in the presence of EGTA; however, the majority of this lipid was in the form of intact phospholipid and triglyceride. These results indicate that release of C20:4 and its oxygenated derivatives from rat PMNs is (1) dependent on the participation ofC9 in the preexisting C5b-8 complex in the cell membrane, and (2) largely dependent on the presence of calcium.     

Nonparticipation of C1q in the decrease of complement activity in the cold in sera of patients with chronic liver diseases

Serum and plasma samples taken simultaneously from 560 patients with various diseases were examined for hemolytic complement activity (CH50) after incubation at 4 degrees C for 20 h. Serum CH50 titers less than 20 U/ml were observed in 39 cases and among them, a difference between serum and plasma CH50 of more than 5 U/ml were observed in 16 cases. Diagnosis of most of them were chronic liver diseases. To analyze the dissociation of CH50 titers between serum and plasma, sequential estimations of CH50 were performed on serum and plasma samples which showed the dissocation incubated at 4 and 37 degrees C. Marked decrease in CH50 titers was obtained in sera but not in plasma incubated at 4 degrees C. In such sera, however, no significant decrease of protein amount and agglutinating activity of C1q was observed. The result could indicate that C1q would not participate in the decrease of serum hemolytic activity in the cold, suggesting an activation of complement other than the classical pathway.     

Level of complement activity and components C1, C4, C2, and C3 in complement response to bacterial challenge in malnourished rats.

In experimentally induced malnutrition in rats, there was no significant difference between the measured level of complement activity of the classical pathway (50% hemolytic complement [CH50]) and that of the alternative pathway (ACH50), although the levels of complement components C1, C4, C2, and C3 were depressed significantly. The complement activity showed a temporary elevation with a peak at 2 or 3 days after bacterial challenge with Staphylococcus aureus in rats, and we call this the complement response. After 3 days, CH50 and C3 in the malnourished rats and ACH50, CH50, and C3 in the well-nourished rats showed a significant increase, and C1, C4, and C2 in both groups tended to elevate. On the basis of these observations, the significance of the elevation of C3 in the complement response to bacterial infection showed a strong influence by enhancing the activation of both the classical and the alternative pathways, since C3 is known to be the junction of both complement pathways. In this way, C3 responded to an earlier stage than did the other components and may contribute to maintaining the body defense system against infection.     

Mouse complement components C4 and Slp act synergistically in a homologous hemolytic C4 assay

Goals of the present study were to compare the hemolytic activities of mouse C4 and Slp in a homologous system and to study a possible interaction between these proteins during complement activation. As reagents for mouse C4 and Slp, we used serum of C4(- / -) knockout C57BL / 6 (C4(-) / Slp(-)) mice and sensitized rabbit erythrocytes as target cells. Sera to be tested contained none, either of the two or both proteins. We found that C4(-) / Slp(+) serum has some hemolytic C4 activity, but less than C4(+) / Slp(-) serum. Comparing C4 activities of C4(+) / Slp(-) and C4(+) / Slp(+) sera, we found a threefold enhanced activity in double-positive serum. Hemolytic C4 levels of mixtures of solely C4- and Slp-sufficient sera did not overlap with expected C4 levels, but rather these sera showed synergy. This explains the enhanced activity of double-positive serum. Similar results were observed for total complement activation. In conclusion, Slp has measurable, but poor C4 activity as compared with mouse C4. Using our homologous system, we showed that the enhanced classical pathway activity of double-positive sera is most probably based on synergy between C4 and Slp. Our results answer an old question as to why C4(+) / Slp(+) mice have higher complement levels than C4(+) / Slp(-) mice.     

A role for C5a in augmenting IgG-dependent histamine release from basophils in chronic urticaria.

BACKGROUND: Histamine release in chronic urticaria is initiated by cross-linking of the alpha subunit of FcepsilonRI by means of IgG antibody, followed by complement activation. OBJECTIVE: We sought to further elucidate the mechanism by which complement augments histamine release and to assess the role of C5a. METHODS: We first quantitated the ability of purified C5a to initiate basophil histamine release and to be inhibited by antibody directed to the C5a receptor. Using this antibody, we quantitated its ability to inhibit histamine release induced by sera from patients with chronic urticaria. We also compared the ability of normal serum, C5-depleted serum, and C5-depleted serum after reconstitution with C5 to augment histamine release by IgG isolated from patients with chronic urticaria. RESULTS: As the concentration of C5a was increased up to 50 ng/mL, the percentage of histamine release increased and reached a plateau of 40% to 50%; this was inhibited by antibody to the C5a receptor. Preincubation of basophils with antibody to the C5a receptor inhibited basophil histamine release from 15 sera tested, with a range of 4% to 39%. Histamine release caused by patient IgG was augmented when normal serum was added but not when C5-depleted serum was substituted for normal serum. Augmentation of histamine release by patient IgG was again obtained when C5-depleted serum was reconstituted with C5. CONCLUSION: Our conclusion is that pathogenic IgG cross-links the IgE receptor directly to cause histamine release, and activation is augmented by complement. C5a is the complement agonist that is responsible for the augmented histamine release.     

Elevated expression of complement C3 protein in chemically induced hepatotumorogenesis in Wistar rats: A correlative proteomics and histopathological study

Liver cancer remains the leading cause of cancer-related mortality worldwide. Early detection of liver cancer is problematic due to the lack of a marker with high diagnosis sensitivity and specificity. The present study was designed to determine the differently expressed proteins at early stage in the serum of animals with liver cancer vis-à-vis controls and figure out the function of the proteins. One-dimensional electrophoresis (1D), two-dimensional electrophoresis (2DE) and liquid chromatography mass spectrometry (LC–MS/MS) were used to screen the serum proteins of liver cancer induced in animals by diethyl nitrosamine (DEN) + 2-acetyl amino fluorine (2-AAF). From optimized 2DE image and computer assisted PD Quest analysis were found to be differentially expressed spots when the serum from normal and treated animals were compared. Among these, one spot was selected whose expression level was higher in DEN + 2-AAF treated animal sera than in adjacent normal animal sera. The target spot was excised from the 2D gel of liver cancer sera and the peptide mass fingerprinting as obtained LC–MS/MS analysis after digesting the chosen protein spot. This was identified to be complement C3 protein. The changes in complement C3 expression level were validated by Western blot analysis. We reported that the changes in complement C3 concentration start at very early stage of tumorogenesis. The fully grown tumors were developed at 120 days and hepatotumorogenesis was confirmed by histopathological examination. This protein may therefore represent a powerful tool in search for candidate biomarkers for HCC.     

Total hemolytic complement (CH50) and its fractions (C3 and C4) in the sera of patients with carcinoma of the oral cavity,uterine cervix,and breast

The total hemolytic complement activity of CH50 and its fractions C3 and C4 was determined in the sera of 196 patients with carcinoma of the oral cavity, 172 patients with carcinoma of the uterine cervix, and 166 patients with breast cancer. The values were compared with those of 18 patients with mammary dysplasia, 32 patients with mild to moderate dysplasia of the cervix, and 100 healthy, normal age- and sex-matched controls. No alterations in CH50, C3, and C4 were observed in the sera of patients with benign lesions, whereas a significant rise in the three factors was observed in all the cancer patients studied. The complement activity increased significantly with the progression of the disease up to stage III and remained persistently elevated thereafter. Patients who had a clinical cure had normal levels of CH50, C3, and C4, whereas the values remained elevated in patients who were still undergoing treatment for residual lesions.     

Determination of the second component of complement (C2) by electroimmunoassay in sera from patients with systemic lupus erythematosus

The concentration of C2 was determined by electroimmunoassay in sera from healthy controls, patients with systemic lupus erythematosus (SLE), their relatives and patients with other diseases. Monospecific anti-human C2 serum was obtained by immunizing rabbits with purified human C2 and then absorbing the rabbit serum with inactivated normal human serum that was made insoluble. In addition, it was shown that human C2 could be purified by means of affinity chromatography on anti-C2 antibody coupled Sepharose. The serum concentration of C2 was 37.8 +/- 5.0 (s.d.) micrograms/ml in healthy controls (n = 133). In patients with SLE, the values were below normal in the active phase and were within normal limits in the inactive phase, showing good correlations with other complement parameters such as CH50, C4, C3 and factor B. C2 concentration was well correlated with C2 haemolytic activity in the inactive phase of SLE, but there was no relationship between the two in the active phase. The mean value of C2 concentration in the relatives of patients with SLE showed no significant difference from that in healthy controls. C2 concentration tended to be high in patients with scleroderma, polymyositis, rheumatoid arthritis, Behçet's disease and aortitis syndrome. However, the values were often low in patients with chronic liver diseases, suggesting a decrease of C2 production in the liver.     

Combined complete C5 and partial C4 deficiency in humans: clinical consequences and complement-mediated functions in vitro

A family is described with two siblings who suffered at different times from a single episode of meningococcal meningitis by Neisseria meningitidis groups B and C, respectively. In the two subjects, hemolytically active fifth component of complement (C5) was not detectable and antigenic C5 was less than 0.05% and less than 0.7% of normal, respectively. Repletion of sera by purified human C5 (70 micrograms/ml) restored total complement hemolytic activities. The asymptomatic first degree family members had C5 levels compatible with a heterozygous state of C5 deficiency. C4 allotyping revealed an inherited partial deficiency (Q0) of C4A and C4B in the family with a combined C4AQ0 and C4BQ0 heterozygous condition in one and C4BQ0 heterozygosity in the other C5 deficient (C5D) subject. To our knowledge, this is the first human kindred with recognized combined C5 and C4 deficiency. No other defect of the humoral and cellular immune system was found in this family, including specific immune response to tetravalent meningococcal vaccine. The effect of partial C4 deficiency on classical pathway function was assessed by inhibition of immune precipitation (IIP) of forming bovine serum albumin (BSA)/anti-BSA immune complexes. Sera from all family members showed normal IIP values, with exception of the subject with combined partial deficiency in C4A, C4B, and complete deficiency in C5. Despite undetectable functional C5 in the C5D sera, the titration of the alternative pathway indicated intact but deficient hemolytic activities when rabbit erythrocytes (EC) were used as indicator cells in the presence of Mg2+ and EGTA in an end-point or kinetic assay. Preincubation of the two sera at 0 degrees C for 60 min with rabbit ECs reduced alternative pathway hemolytic activity by 24 and 100%, respectively. When rabbit ECs were replaced by guinea pig ECs no alternative pathway function could be measured. The results indicate that the apparent functional activity of the alternative pathway in C5D sera strongly depends on a factor(s) present in such serum and/or on the detection system used. We conclude that the two C5D individuals of the family reported here may not have sufficient C5 activity to provide efficient protection against Neisserial infections in conditions where complement functions beyond C3 opsonic activity are required in vivo.     

Plasma C3d/C3 quotient as a parameter for in vivo complement activation

Plasma levels of C3 and C3d in 30 healthy donors and 58 patients with systemic lupus erythematosus were determined by rocket immunoelectrophoresis and Con-A affinoimmunoelectrophoresis. Significantly decreased levels of C3 were found in approximately 50% of the SLE sera. Slight increases of free C3d were found in 55%, and marked increases in 9% of the SLE sera; the remaining SLE sera did not show increased C3d levels. When results were expressed as quotients of plasma C3d/C3, a significant pattern emerged and 70% of the SLE sera clearly fell outside the normal range. 10% of the SLE sera had normal C3d/C3 indices but had markedly depressed C3 levels. We conclude that in cases where total serum C3 is not markedly reduced (less than 60% of normal), the C3d/C3 quotient may be a more sensitive parameter for assessing in vivo complement activation than C3 or C3d determinations alone.